L19_regulation of the Immune response Flashcards
What is tolerance?
The lack of response to a specific antigen.
Is tolerance innate or acquired?
acquired
What are the 2 major mechanisms of tolerance? What are the other 3
1 Deletion of reactive cells. 2 Inactivation of reactive cell: ANERGY 3 Functional Deletion 4 Generation of Suppressor or Regulatory Tcells (Treg) 5 Blocking of presentation or Activation
Is anergy reversible?
No
What is the major difference in the way T-reg cells interact with APC compared to other T-cells
It interacts with B7 via CTLA-4 instead of CD28 and then they send suppression signals to the T-cell
How are T-Cells turned off after an immune response?
They start up-regulating CTLA-4 after a certain period of time and down-regulate CD28. CTLA-4 binds B7 with higher affinity and sends a suppressing signal to the cell.
What are the mechanisms of tolerance in B cells?
1 Clonal Deletion
2 Clonal abortion/clonal Anergy
3 Functional Deletion
Where does clonal deletion take place for B-Cells?
Is the level of deletion at this site higher or lower than what you see in the thymus with T-cells?
The Bone Marrow. Less deletion than in thymus with T-Cells
If an immature B-cell in the bone marrow reacts with multivalent self antigen what happens? what it if reacts with solubilized self antigen?
Multivalent - apoptosis
Solubilized - Anergic B-cell in periphery (IgD predominately expressed)
Describe which physical forms of an antigen favor an immune response and which favor tolerance
Immune- Large, aggregated, complex molecule
Tolerance- Soluble, aggregate-free, relatively smaller, less complex molecules not processed by APC
Describe the routes of antigen administration that favor immune response and those that favor tolerance
Immune- SQ or IM
Tolerance- Oral or sometimes IV
Describe the dose of an antigen that favors immune response versus tolerance
Immune- optimal dose
Tolerance- Very large or sometimes very small dose
Describe the age of responding animal that favors an immune response versus tolerance
Immune- Older and immunologically mature
Tolerance- Newborn, immunologically immature
Describe the differentiation state of cells that favor immune response versus tolerance
Immune- Fully differentiated cells; memory T and memory B
Tolerance- Relatively undifferentiated: B cells with only IgM, thymocytes
What surface markers do Regulatory T-Cells Have?
FoxP3, CD25, CD4